Guanfacine Hydrochloride Extended-Release for Attention Deficit Hyperactivity Disorder: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines

Key Message

Since the previous recommendations issued by the Canadian Drug Expert Committee (CDEC) on September 2014, four systematic reviews (including pairwise meta-analyses and network meta-analyses of direct and indirect evidence), one randomized controlled trial, and one guideline have been published regarding the use of guanfacine hydrochloride extended-release (GXR) for the treatment of attention deficit-hyperactivity disorder (ADHD) in children and adolescents.All included studies reported significant improvements in subjective ADHD rating scales as well as scales in executive function when using GXR compared to placebo for treatment in children and adolescents with ADHD. This demonstrates improvements not only in ADHD symptoms but on social functioning, which is also integral to ADHD management. No studies were found which provided direct evidence comparing GXR to active treatments; however, four studies with indirect analyses were included which allowed comparisons to be made. There were no significant differences between GXR and active ADHD treatments; however, it was concluded that GXR may have a moderate effect on efficacy compared to active treatments. These clinical studies may further support evidence of the use of GXR in children with ADHD who are inadequately controlled with methylphenidate or an amphetamine.All systematic reviews found that when GXR was compared to placebo, there was a significantly higher incidence of discontinuations due to treatment-emergent adverse events. Four systematic reviews also found a higher incidence of discontinuations due to treatment-emergent adverse events when GXR was compared against other active treatments via direct and indirect comparisons. The most commonly reported adverse effects have been reported as abdominal pain, fatigue, and headaches.One included guideline issued a recommendation based on moderate quality evidence on the use of GXR as monotherapy or in combination with a psychostimulant for the management of oppositional behavior in children and adolescents with ADHD, with or without oppositional defiant disorder.However, the robustness of evidence included in this report for the use of GXR as monotherapy relative to other treatments for ADHD was low, and no relevant economic evaluations were identified. Several gaps in the evidence identified by CDEC in 2014 are remaining, such as the long-term efficacy and safety of GXR as adjunctive therapy to psychostimulants in children with ADHD.